We are studying the activation of the mammalian genome. Our object is to identify genes which influence the expression of one protein, the enzyme beta-galactosidase. A screen of inbred and mutant mice has led to the identification of the three such genetic loci which influence the amount of enzyme protein present in mouse tissue. One of these genes produces a doubling in the amount of beta-galactosidase protein in all mouse tissues. The second genetic locus has a generalized effect on excretion of lysosomes by the kidney. The third gene affects liver beta-galactosidase at a single period of development; this may be a mutation within a developmental program. Biochemical and immunological studies in progress are designed to measure the in vivo rates of beta-galactosidase synthesis and degradation in variant mice, and to ascertain the mechanism of action of these three genes. BIBLIOGRAPHIC REFERENCES: H. Tanaka, M. Meisher and K. Suzuki, Activity of Human Hepatic beta-Galactosidase Towards Natural Glycosphingolipid Substrates, Biochim. Biophys. Acta, 390, 452-463 (1975). S. Tomino and M. Meisler, Biochemical and Immunological Studies of Purified Mouse beta-Galactosidase. J. Biol. Chem., 250, 7752-7758 (1975).